The goal of this proposed research is to understand the role of highly conserved domains within the collagen IV molecule. Collagen IV is one of the most abundant proteins present in basement membranes. The most common collagen IV molecule is a trimer of the composition, alpha1(IV)2alpha2(IV). Collagen IV is important developmentally since mutations in alpha1 and alpha2(IV) of C. elegans cause embryonic lethality and mutations in human alpha3-alpha5(IV) genes are the molecular defects in the X-linked and autosomal form of Alport syndrome. Highly conserved features (C. elegans to humans) on collagen IV include the integrin alpha1beta1 binding site, cysteine residues, and an asparagine-linked glycosylation site. The role of these conserved amino acids in collagen IV function will be assessed in vivo by producing transgenic C. elegans animals. The ability of the collagen IV transgenes to rescue the embryonic lethality of a null mutant will allow a measure of function of the specific mutated sites. C. elegans is an excellent system to study the phenotypic effects of generated mutations. It has defined cell linkages, detailed anatomy is visible through a transparent cuticle and production of transgenic animals is feasible. Also antibodies are available to analyze phenotypic defects that result from specific mutations in collagen IV.